Dietary trans-10, cis-12-conjugated linoleic acid (trans-10, cis-12-CLA) fed to obese and nonobese rodents reduces body fat but leads to greater liver mass due to steatosis. The molecular mechanisms accompanying such responses remain largely unknown. Our study investigated the effects of chronic low trans-10, cis-12-CLA supplementation on hepatic expression of 39 genes related to metabolism, inflammation, and stress in growing mice. Feeding a diet supplemented with 0.3% trans-10, cis-12-CLA (wt/wt basis) for 6 weeks increased liver mass and concentration of long-chain fatty acids (LCFAs) in liver, while adipose tissue mass decreased markedly. These changes were accompanied by greater expression of genes involved in LCFA uptake (Cd36), lipogenesis, and triacylglycerol synthesis (Acaca, Gpam, Scd, Pck1, Plin2). Expression of these genes was in line with upregulation of the lipogenic transcription factor Srebf1. Unlike previous studies where higher >0.50% of the diet) doses of trans-10, cis-12-CLA were fed, we found greater expression of genes associated with VLDL assembly/secretion (Mttp, Cideb), ketogenesis (Hmgcs2, Bdh1), and LCFA oxidation (Acox1, Pdk4) in response to trans-10, cis-12-CLA. Dietary CLA, however, did not affect inflammation- and stress-related genes. Results suggested that a chronic low dose of dietary CLA increases liver mass and lipid accumulation due to activation of lipogenesis and insufficient induction of LCFA oxidation and VLDL assembly/secretion. 1. Introduction Conjugated linoleic acid (CLA) refers to a group of conjugated octadecadienoic acid isomers derived from linoleic acid (LA), a long-chain fatty acid (LCFA) that contains 18 carbons and 2 double bonds [1]. Antilipogenic effects of dietary CLA mixtures with a 1？:？1 ratio of trans-10, cis-12-CLA and cis-9, trans-11-CLA were initially observed in several lines of mice, and later work using purified isomer preparations clearly showed that trans-10, cis-12-CLA was responsible for delipidation [2, 3] (summarized in Table 1). Studies also have revealed unfavorable metabolic effects of trans-10, cis-12-CLA associated with an increased oxidative stress and inflammation [4] often coupled with hepatic steatosis [5–9]. As trans-10, cis-12-CLA supplementation reduces the amount of adipose tissue, several studies suggest that much of the increased liver mass may be explained by accumulation of lipid [10, 11] derived from breakdown of adipose tissue stores [12, 13]. Table 1: Summary of the changes in liver mass, liver TG, and adipose tissue mass observed in previous mouse studies feeding
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